Overview

This trial is active, not recruiting.

Conditions reumatoid arthritis, cardiovascular diseases
Sponsor Radboud University
Start date September 2012
End date December 2014
Trial size 48 participants
Trial identifier NCT02130076, IMM11-0103

Summary

Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular events. This increased risk is thought to be driven by inflammation-induced endothelial dysfunction, an initial step in atherogenesis. Treatment with TNFalpha inhibitors (TNFi) improve endothelial function in patients with RA. Discontinuation of TNFi could therefore worsen endothelial function even in the absence of recurrence of systemic inflammation or reactivation of arthritis. If stopping TNFi results in worsening of endothelial function this would strongly suggest a higher cardiovascular risk in association with TNFi-wthdrawal

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Observational model case control
Time perspective prospective
Arm
Patients with stable RA stopping TNF inhibition
Patients with stable RA continuing TNFi therapy

Primary Outcomes

Measure
Response to acetylcholine
time frame: 6 months

Secondary Outcomes

Measure
TNFi withdrawal and response to nitroprusside
time frame: 6 months
VCAM and SCAM
time frame: 6 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Informed consent for POEET trial and this additional study - On stable medication (except for TNFi-therapy) Exclusion Criteria: - Uncontrolled hypertension (RR > 140/90 mmHg average of three measurements at screening after 5 minutes of supine rest) - Diabetes mellitus - Heart failure or any other cardiovascular disease that is expected to induce changes in cardiovascular medication during the study period. - Expected to start or change medication that can alter endothelial function (lipid lowering drugs, blood pressure lowering drugs, NSAIDs, immunosuppressive therapy other than TNFi drugs)

Additional Information

Official title The Effect of Interruption of TNFi on Endothelial Function in Patients With Rheumatoid Arthritis
Description Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular events. This increased risk is thought to be driven by inflammation-induced endothelial dysfunction, an initial step in atherogenesis. Both systemic as well as local (intra-arterial) treatment with anti-TNF-antibody therapy improves endothelial function in patients with vasculitis or RA as reflected by the vasodilator response to intra-arterially infused acetylcholine. Also other vascular functions that are (at least partially) endothelium-dependent such as flow-mediated dilation of the brachial artery and pulse wave velocity are improved when active RA patients are being treated with methotrexate plus TNFi, i.e. infliximab or etanercept. ( Therefore one may hypothesize that when TNFi therapy is stopped, endothelial function may worsen even in the absence of recurrence of systemic inflammation or reactivation of arthritis. Endothelial function tests are a marker of long-term cardiovascular mortality. If stopping TNFi results in worsening of endothelial function this would strongly suggest a higher cardiovascular risk in association with TNFi-wthdrawal. These findings would indicate an important drawback for stopping TNFi in RA patients. To date it is unclear whether the worsening of endothelial function occurs within half a year following the (successful) cessation of TNFi, whether this decline occurs simultaneously, or prior to RA exacerbation and whether this deterioration process is delayed by additional use of statin and/or ACEi. To improve cardiovascular prognosis in RA significantly it is important to increase our knowledge regarding these processes.
Trial information was received from ClinicalTrials.gov and was last updated in May 2014.
Information provided to ClinicalTrials.gov by Radboud University.